Prognostic stratification of high-risk gastrointestinal stromal tumors in the era of targeted therapy
Prognostic stratification of high-risk gastrointestinal stromal tumors in the era of targeted therapy
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DOI：
10.1097/sla.0b013e3181724f9d
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发表时间：
2008-06-01
影响因子：
9
通讯作者：
Kim, Kyoung-Mee
中科院分区：
文献类型：
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作者：
Park, Cheol Keun;Lee, Eui Jin;Kim, Kyoung-Mee
背景：最近，一项辅助伊马替尼治疗原发性ro切除的中高危胃肠道间质瘤（gist）的试验显著提高了无复发生存率。但识别出复发几率较高的患者，可以减少经济损失，防止辅助治疗带来的不良副作用。方法：对93例高危gist患者组织标本进行p16、CD34、CD44蛋白表达及KIT、PDGFRA基因突变检测。通过单因素和多因素分析，将临床病理、免疫组织化学和突变结果与临床结果进行比较。结果：KIT突变75例（81%），其中外显子11缺失46例，影响密码子557 ~ 558的缺失31例。在小肠GIST中检测到KIT外显子9上一个新的12bp缺失突变（KHNG484-488）。对于无复发生存率，单因素分析中，R0切除、器官局限性疾病分期和女性是较好的预后因素，多因素分析中，疾病分期是唯一预测复发的因素（P = 0.02）。在总生存率中，突变类型、突变存在、gist位置和有丝分裂在单变量分析中具有显著性。多变量分析后，有丝分裂计数和KIT突变的存在与独立的预后因素相对应。此外，有丝分裂、KIT外显子I I缺失突变和影响外显子557-558的缺失预测ro切除的高危gist的复发（P < 0.05）。结论：高危间质瘤间质瘤的预后分层将有助于鉴别高危间质瘤患者，哪些患者可能受益于辅助治疗。
Background: Recently, a trial of adjuvant imatinib for primary RO-resected intermediate and high-risk gastrointestinal stromal tumors (GISTs) significantly improved recurrence-free survival. But identifying patients having higher chances of recurrence will reduce economic losses and prevent adverse side effects caused by adjuvant treatment.Methods: Tissue samples from 93 patients with high-risk GISTs were studied for p16, CD34, and CD44 protein expression and mutations of KIT and PDGFRA gene. Clinicopathologic, immunohistochemical, and mutation results were compared with clinical outcome by univariate and multivariate analyses.Results: KIT mutations were observed in 75 cases (81%) including 46 exon 11 deletion mutations and 31 deletions affecting codons 557-558. A novel 12 bp deletion mutation (KHNG484-488) on KIT exon 9 was detected in a small intestinal GIST. For recurrence-free survival, R0 resection, organ-confined disease stage, and female sex are better prognostic factors in univariate analysis and disease stage was the only factor predicting recurrence (P = 0.02) in multivariate analysis. In overall survival, mutation types, presence of mutation, location of GISTs, and mitosis were significant by univariate analysis. After multivariate analysis, mitotic counts and presence of KIT mutation corresponded to independent prognostic factors. Moreover, mitosis, KIT exon I I deletion mutation, and deletions affecting exon 557-558 predict recurrence in RO-resected high-risk GISTs (P < 0.05).Conclusion: Prognostic stratification in high-risk GISTs will help identify patients with high-risk GIST who may benefit from adjuvant therapy.